B12 Regulation of PUFA Synthesis Grant uri icon

abstract

  • Abstract Age-related cognitive decline is strongly associated with increase in inflammation and oxidative stress. There is also accumulating evidence that long-term dietary deficiencies, namely vitamin B12 (B12) and essential fatty acids might also contribute to loss of myelination maintenance. The major aims of this proposal are designed to investigate the benefit of combined supplementation of B12 coupled with n-3 polyunsaturated fatty acids (PUFAs), as opposed to their individual administration, in reducing the basic pro-inflammatory mechanisms thought to underly age-related neurodegenerative disorders. Recent evidence suggests that PUFA synthesis is regulated to some extent by methyl group metabolism and epigenetic modifications. Thus, the specific hypothesis to be tested is that B12 is important for the synthesis and efficacy of long chain n-3 fatty acids, EPA and DHA bioactive lipids with known anti-inflammatory function. To address this hypothesis, an in vitro model using macrophage cell line will be used. The first specific aim is to address whether B12 or the combined supplementation of B12 plus ?-linolenic acid (ALA) will influence macrophage pro-inflammatory and/or anti-inflammatory responses. In the second aim, the expression of integral elongases and desaturases involved in PUFA synthesis as well as the concentration of n-3 and n-6 PUFAs will be assessed in macrophages following exposure to B12 or the combined exposure of B12 and PUFAs. One important outcome would be pilot data linking epigenetic regulation of PUFA synthesis pathway to inflammatory mechanisms. The most important outcome would be the clinical significance of combined supplementation of B12 plus n-3 PUFAs acting synergistically to reduce inflammation. We expect that this interaction between B12 and PUFA synthesis are not limited to only inflammatory cells but other cells and tissues such as mammary or cortical grey matter where complex PUFA formation takes place that are integral to overall human health.

date/time interval

  • September 2020 - May 2023